- Synthesis and Electrical Properties of Derivatives of 1,4-bis(trialkylsilylethynyl)benzo[2,3-b:5,6-b′]diindolizines
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A new class of nitrogen-containing arene organic semiconductors incorporating fused indolizine units is described. This system, though having a zigzag shape, mimics the electronic properties of its linear analogue pentacene as a result of nitrogen lone pair incorporation into the π-electron system. Solubilizing trialkylsilylethynyl groups were employed to target crystal packing motifs appropriate for field-effect transistor devices. The triethylsilylethynyl derivative yielded hole mobilities of 0.1 cm2 V-1 s-1 and on/off current ratios of 105.
- Granger, Devin B.,Mei, Yaochuan,Thorley, Karl J.,Parkin, Sean R.,Jurchescu, Oana D.,Anthony, John E.
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- 6,5-Fused Ring, C2-Salvinorin Ester, Dual Kappa and Mu Opioid Receptor Agonists as Analgesics Devoid of Anxiogenic Effects**
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Current common analgesics are mediated through the mu or kappa opioid receptor agonism. Unfortunately, selective mu or kappa receptor agonists often cause harmful side effects. However, ligands exhibiting dual agonism to the opioid receptors, such as to mu and kappa, or to mu and delta, have been suggested to temper undesirable adverse effects while retaining analgesic activity. Herein we report an introduction of various 6,5-fused rings to C2 of the salvinorin scaffold via an ester linker. In vitro studies showed that many of these compounds have dual agonism on kappa and mu opioid receptors. In vivo studies on the lead dual kappa and mu opioid receptor agonist demonstrated supraspinal thermal analgesic activity while avoiding anxiogenic effects in male mice, thus providing further strong evidence in support of the therapeutic advantages of dual opioid receptor agonists over selective opioid receptor agonists.
- Akins, Nicholas S.,Ashpole, Nicole M.,Dudhipala, Narendar,Harris, Hannah M.,Keasling, Adam W.,Kim, Seong Jong,Le, Hoang V.,Majumdar, Soumyajit,Mishra, Nisha,Paris, Jason J.,Zjawiony, Jordan K.
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- Propylphosphonic acid anhydride–mediated amidation of Morita–Baylis–Hillman–derived indolizine-2-carboxylic acids
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Propylphosphonic acid anhydride has been successfully used as a coupling agent in the synthesis of a series of indolizine-2-carboxamido derivatives from indolizine-2-carboxylic acid and its 3-acetylated analogue. The acid substrates were obtained by sapon
- Sekgota, Khethobole C,Isaacs, Michelle,Hoppe, Heinrich C,Seldon, Ronnett,Warner, Digby F,Khanye, Setshaba D,Kaye, Perry T
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p. 674 - 678
(2021/03/31)
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- Chiral Phosphoric Acid Catalyzed Desymmetrization of Cyclopentendiones via Friedel–Crafts Conjugate Addition of Indolizines
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An organocatalytic highly diastero- and enantioselective Friedel–Crafts conjugate addition of indolizines to prochiral cyclopentenediones has been successfully developed. This desymmetric transformation provides a direct access to the desired indolizine-substituted cyclopentanediones in yields of 62–91% and excellent stereoselectivities. The utility of the approach was demonstrated by diverse late-stage functionalizations through reduction or oxidation. Importantly, the direct sp2 C–H functionalization with nitromethane in one-pot process resulted in the indolizine-linked axially chiral styrene bearing a remote chiral center.
- Ni, Qijian,Zhu, Zhiming,Fan, Yanjun,Chen, Xiaoyun,Song, Xiaoxiao
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p. 9548 - 9553
(2021/12/14)
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- NOVEL INDOLIZINE-2-CARBOXAMIDES ACTIVE AGAINST THE HEPATITIS B VIRUS (HBV)
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The present invention relates generally to novel antiviral agents. Specifically, the present invention relates to compounds which can inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV replication cycle, compositions comprising such compounds, methods for inhibiting HBV viral replication, methods for treating or preventing HBV infection, and processes and intermediates for making the compounds.
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- NOVEL OXALYL PIPERAZINES ACTIVE AGAINST THE HEPATITIS B VIRUS (HBV)
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The present invention relates generally to novel antiviral agents. Specifically, the present invention relates to compounds which can inhibit the protein(s) encoded by hepatitis B virus (HBV) or interfere with the function of the HBV replication cycle, compositions comprising such compounds, methods for inhibiting HBV viral replication, methods for treating or preventing HBV infection, and processes and intermediates for making the compounds.
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- Discovery of fused heterocyclic carboxamide derivatives as novel α7-nAChR agonists: Synthesis, preliminary SAR and biological evaluation
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The α7 nicotinic acetylcholine receptor (α7 nAChR) has emerged as a promising therapeutic target for schizophrenia. In our previous work, a novel series of α7-nAChR agonists bearing scaffold of indolizine were discovered. To explore the effect of aromaticity on the activity and find more active agents, herein, fused heterocyclic carboxamide derivatives were designed and synthesized in this study. Based on the evaluation by two-electrode voltage clamp in Xenopus oocytes, 27 of the synthesized compounds showed obvious agonism of α7 nAChR. Particularly, compounds 10a and 10e showed significantly higher Emax than EVP-6124. The result illustrated the importance of aromaticity to the activity of agonism. Compound 10a, which showed EC50 of 1.88 μM and Emax of 72.4%, was further characterized comprehensively, including co-application with type II positive allosteric modulator PNU-120596, selectivity with other closely related ligand-gated ion channel, etc. The results showed that 10a showed moderate selectivity over other subtypes such as α4β2 and α3β4 nAChR. 10a evoked α7-like currents that were inhibited by MLA and enhanced in the presence of the α7 PAM PNU-120596. The analysis of binding mode and understanding of structure-activity relationship provided insights to develop more potent novel α7-nAChR agonists.
- Xue, Yu,He, Xiaomeng,Yang, Taoyi,Wang, Yuxi,Liu, Zhenming,Zhang, Guisen,Wang, Yanxing,Wang, Kewei,Zhang, Liangren,Zhang, Lihe
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- Ruthenium(II) Catalysed Highly Regioselective C-3 Alkenylation of Indolizines and Pyrrolo[1,2-a]quinolines
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Discovered the Ruthenium(II) catalysed highly stereo- and regioselective protocol for the oxidative C-3 alkenylation of indolizines and pyrrolo[1,2-a]quinolines. The methodology represents the first example for the directing group assisted C–C bond formation reaction of the indolizines. Under mild reaction conditions, this method provides an ample substrate scope to produce C-3 alkenyl indolizines in excellent to moderate yields. However, pyrrolo[1,2-a]quinolines underwent alkenynation at elevated temperature to furnish C-3 alkenyl derivatives. The functionalized indolizines were selectively reduced to obtain their saturated derivatives.
- Jadhav, Pankaj Pandit,Kahar, Nilesh Machhindra,Dawande, Sudam Ganpat
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supporting information
p. 7831 - 7835
(2019/12/24)
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- Catalytic Asymmetric Conjugate Addition of Indolizines to α,β-Unsaturated Ketones
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A catalytic enantioselective conjugate addition of indolizines to enones is described. The chiral phosphoric acid (S)-TRIP activates α,β-unsaturated ketones, thereby promoting an enantioface-differentiating attack by indolizines. Using this reaction, several alkylated indolizines were synthesized in good yields and with enantiomeric ratios of up to 98:2.
- Correia, José Tiago Menezes,List, Benjamin,Coelho, Fernando
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p. 7967 - 7970
(2017/06/27)
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- Synthesis and biological activities of indolizine derivatives as alpha-7 nAChR agonists
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Human α7 nicotinic acetylcholine receptor (nAChR) is a promising therapeutic target for the treatment of schizophrenia accompanied with cognitive impairment. Herein, we report the synthesis and agonistic activities of a series of indolizine derivatives targeting to α7 nAChR. The results show that all synthesized compounds have affinity to α7 nAChR and some give strong agonistic activity, particularly most active agonists show higher potency than control EVP-6124. The docking and structure-activity relationship studies provide insights to develop more potent novel α7 nAChR agonists.
- Xue, Yu,Tang, Jingshu,Ma, Xiaozhuo,Li, Qing,Xie, Bingxue,Hao, Yuchen,Jin, Hongwei,Wang, Kewei,Zhang, Guisen,Zhang, Liangren,Zhang, Lihe
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- 2-indolizine Carbamoyl amine compound and its preparation and use
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The invention discloses a novel 2-indolizine formylamine derivative. The general formula of the novel 2-indolizine formylamine derivative is as shown in a formula (I), wherein the definition of R is specified in the specification. In addition, the inventi
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Paragraph 0112; 0152-0155
(2020/02/07)
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- Selective hydrogenation of indolizines: An expeditious approach to derive tetrahydroindolizines and indolizidines from Morita-Baylis-Hillman adducts
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In this study, we describe the hydrogenation of indolizines derived from Morita-Baylis-Hillman adducts. We demonstrate that functionalized tetrahydroindolizines and indolizidines can be prepared selectively, at low pressure, by simply adjusting the acidity of the medium. Using this simple and straightforward strategy, substituted tetrahydroindolizines and indolizidines were obtained diastereoselectively in high yield.
- Teodoro, Bruno V. M.,Correia, José Tiago M.,Coelho, Fernando
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p. 2529 - 2538
(2015/03/18)
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- HETEROARYL PYRIDONE AND AZA-PYRIDONE COMPOUNDS AS INHIBITORS OF BTK ACTIVITY
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Heteroaryl pyridone and aza-pyridone compounds of Formula I are provided, where one or two of X, X, and Xare N, and including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk kinase, and for treating immune disorders such as inflammation mediated by Btk kinase. Methods of using compounds of Formula I foranddiagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
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- ALKYLATED PIPERAZINE COMPOUNDS
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Alkylated piperazine compounds of Formula I are provided, including stereoisomers, tautomers, and pharmaceutically acceptable salts thereof, useful for inhibiting Btk kinase, and for treating immune disorders such as inflammation mediated by Btk kinase. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, and treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.
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- Microwave-assisted convenient syntheses of 2-indolizine derivatives from Morita-Baylis-Hillman adducts: New in silico potential ion channel modulators
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In this work, a microwave-assisted synthesis study by microwave irradiation to produce indolizine-2-carbonitrile and indolizine-2-carboxylate in good to high yields (70 and 81percent, respectively) in one step from Morita-Baylis-Hillman adducts (MBHA) is presented. These compounds were subsequently transformed to high yields (94 to 100percent, respectively) in three 2-indolizine derivatives. The five synthesized compounds were designed in silico aiming to present potential selective activities as ion channel modulators. These activities were suggested by the score values using Molinspiration Cheminformatics program.
- Cunha, Saraghina M.D.,De Oliveira, Ramon G.,Vasconcellos, Ma?rio L.A.A.
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p. 432 - 438
(2013/08/25)
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- Indolizine studies, part 5: Indolizine-2-carboxamides as potential HIV-1 protease inhibitors[1]
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1,1-Carbonyldiimidazole-promoted coupling of Baylis-Hillman-derived indolizine-2-carboxylic acids with a range of amine and amino acid derivatives has provided access to the corresponding carboxamides in moderate to excellent yield. Copyright
- Tukulula, Matshawandile,Klein, Rosalyn,Kaye, Perry T.
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scheme or table
p. 2018 - 2028
(2010/09/05)
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- A mild preparation of substituted indolizines and indole from simple aromatic precursors using (trimethylsilyl)diazomethane
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A mild and convenient synthesis of substituted indolizines from readily available 2-(pyridin-2-yl)acetyl derivatives using (trimethylsilyl)diazomethane is described. The extension of this methodology to the synthesis of indole from 2-aminobenzaldehyde is also reported.
- Zhu, Liusheng,Vimolratana, Marc,Brown, Sean P.,Medina, Julio C.
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p. 1768 - 1770
(2008/09/18)
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- Analysis of the concerted metalation-deprotonation mechanism in palladium-catalyzed direct arylation across a broad range of aromatic substrates
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The concerted metalation-deprotonation mechanism predicts relative reactivity and regioselectivity for a diverse set of arenes spanning the entire spectrum of known palladium-catalyzed direct arylation coupling partners. An analysis following an active st
- Gorelsky, Serge I.,Lapointe, David,Fagnou, Keith
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supporting information; experimental part
p. 10848 - 10849
(2009/02/05)
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- Indolizine studies. Part 4. Kinetics and mechanism for the formation of indolizines via thermal cyclisation of 2-pyridyl derivatives
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The influence of substituents and temperature on the thermal cyclisation of 3-acetoxy-2-methylene-3-(2-pyridyl)propanoic esters and analogues has been explored using 1H NMR spectroscopy, and mechanistic proposals for the formation of the resulting indolizines are presented.
- Deane, Philip O.,George, Rosemary,Kaye, Perry T.
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p. 3871 - 3876
(2007/10/03)
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- Indolizine Studies. Part 2. Synthesis and NMR Spectroscopic Analysis of 2-Substituted Indolizines
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Thermal cyclisation of 3-acetoxy-3-(2-pyridyl)-2-methylenepropionate esters and related compounds provides convenient access to 2-substituted indolizines.Detailed one- and two-dimensional NMR spectroscopic analysis of the title compounds has facilitated interpretation of their 1H and 13C NMR spectra.
- Bode, Moira L.,Kaye, Perry T.
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p. 1809 - 1814
(2007/10/02)
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- A New Synthesis of Indolizines via Thermal Cyclisation of 2-Pyridyl Derivatives
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Thermal cyclisation of methyl 3-hydroxy-2-methylene-3-(2-pyridyl)propanoate (3a) and analogues affords convenient access to indolizine derivatives.
- Bode, Moira L.,Kaye, Perry T.
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p. 2612 - 2613
(2007/10/02)
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